Figure 3.

Epigenetic remodeling through hypoxic-dependent pathways. The accumulation of epigenetic alterations is characteristic of a hypoxic microenvironment in tumors. (A) Epigenetic changes. Briefly, is has been intensively reported that after HIF-1α stabilization, decreased DNA methyltransferases (DNMTs) activity correlates with oncogene activation. Conversely, HCADs and KDMs increased activity induces overall genomic instability. (B) Histone modifications. Histone methylation, depending on the residue, induces gene transcription activation or repression. Specifically, H3K4me3 and H3K36me2/3 are often correlated with transcriptional activation, whereas H3K9me3 and H3k27me3 are associated with transcriptional repression, both implicated tumor development and progression. Abbreviations: Ac—acetylation; DNMTs—DNA methyltransferases; HDACs—Histone deacetylases; HIF—Hypoxia-inducible factors; KDMs—Histone lysine demethylases; Me—methylation; PHD—Prolyl hydroxylases; TS—Tumor suppressor.